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We report an observation of the 6s5d1D2 – 5d2 1D2 forbidden transition in Ba atom by means of high-resolution atomic-beam laser spectroscopy. Stark shifts and splittings of this forbidden transition were measured for 136Ba and 138Ba using the Stark-induced interference method, increasing as the applied electric field increases. From measured spectra at various electric fields, scalar and tensor polarizabilities of the forbidden transition were obtained and found to be much larger than those of other levels. The forbidden transition with large electric polarizabilities, resulting from strong mixing between the two closely lying levels of 5d2 1D2 and 5d6p1D2, provides a good candidate for atomic parity non-conservation study. [ABSTRACT FROM AUTHOR]

Rainbow particle tracking velocimetry can be used to measure 3D3C flow velocity vectors with a single color camera. The particle depth position is calculated from the hue degree of a particle color. A liquid–crystal display (LCD) projector can be used conveniently as a light source of the color pattern in place of the spectral diffraction of white light. Another advantage of using an LCD projector is the ability to change the RGB components of the color pattern. In this study, the rainbow color pattern was modified to increase available color. Colors with the same hue degree but different saturations were used in the color pattern. Using color space enhanced positional resolution in the color change direction. The parameters of new color patterns were number of cycles, saturation continuity and range of color space. They were designed and their performances were compared. The effective resolution in color change direction enhanced 2.4 times from original patten (single cycle rainbow), and velocity vector acquisition rate improved, in particular, for the range of small amount movement per step. [ABSTRACT FROM AUTHOR]

Background: Lateral node metastasis confers a poor prognosis in rectal cancer. Several multidisciplinary treatments have been proposed with favorable outcomes. However, appropriate neoadjuvant/adjuvant treatments or follow-up plans based on information about the probable recurrence site have not been specified. We aimed to clarify the distinctive features of recurrence patterns for lateral node-positive low rectal cancer according to the lateral and mesorectal lymph node status. Methods: We retrospectively analyzed 508 patients with stage III low rectal cancer who underwent lateral node dissection. We investigated the impact of lateral and mesorectal lymph node status on site-specific recurrence rates and patient survival. Results: Analyses for relapse-free survival revealed the prognostic impact of lateral node positivity in stage III low rectal cancer (p < 0.0001). Lateral node-positive patients exhibited higher risk of overall recurrence, local recurrence, and recurrence in extra-regional nodes than lateral node-negative patients (p < 0.0001, p = 0.001, and p < 0.0001, respectively). However, lateral node positivity was not statistically associated with a hematogenous recurrence rate. In lateral node-positive patients, both tumor-node-metastasis (TNM)-N status and number of lateral nodes involved were revealed as significant prognostic factors (p < 0.0001, both). In addition, the number of lateral nodes involved could be a discriminatory indicator of probabilities of local recurrence and recurrence in extra-regional nodes (p = 0.02, and p < 0.0001, respectively). Conclusions: Lateral node-positive low rectal cancer exhibits higher local recurrence and extra-regional node recurrence rates that correlate with the number of lateral nodes involved. [ABSTRACT FROM AUTHOR]

DESTINY-CRC01 (NCT03384940) was a multicentre, open-label, phase 2 study that investigated the safety and efficacy of trastuzumab deruxtecan (T-DXd) in patients with human epidermal growth factor receptor 2 (HER2)-expressing metastatic colorectal cancer (CRC). The present exploratory biomarker analysis aims to investigate relationships between biomarkers and clinical outcomes in patients with HER2-positive (immunohistochemistry [IHC] 3+ or IHC 2+ and in situ hybridization [ISH] positive) Cohort A (N = 53) of DESTINY-CRC01. Higher levels of HER2 biomarkers in baseline tissue and liquid biopsies, including HER2 status (IHC/ISH), HER2/CEP17 ratio, HER2 ISH signals, HER2 H-score, plasma HER2 (ERBB2) amplification status, HER2 adjusted plasma copy number, and HER2 extracellular domain correlate with antitumor activity (indicated by objective response rate, progression-free survival, and overall survival) of T-DXd. Baseline circulating tumor DNA (ctDNA) analysis suggests antitumor activity of T-DXd in patients who had baseline activating RAS, PIK3CA, or HER2 mutations detected in ctDNA. The phase 2 trial, DESTINYCRC01, previously demonstrated durable activity of trastuzumab deruxtecan (T-DXd) in patients with HER2-positive metastatic colorectal cancer refractory to standard treatment. Here, the authors report the exploratory analysis of the DESTINY-CRC01 trial investigating markers of response or resistance to T-DXd. [ABSTRACT FROM AUTHOR]

Mast cells (MCs) are tissue-resident cells of hematopoietic origin that play an important role in host's defense mechanism against nematodes. However, excessive activation of these cells contributes to the development of certain allergic diseases. Immunoglobin E (IgE) is one of the well-known molecules that activate MCs. Even in the absence of specific antigens, the binding of highly cytokinergic IgE to FcεRI on MCs prolongs their survival and induces cytokine production without enhancing their degranulation. In the present study, we examined the effects of the members of the interleukin-10 (IL-10) family of cytokines on IgE-mediated MCs functions. The receptors including Il10r1, Il10r2, and Il20r2, but not Il20r1, Il22r1 or Il28r1, were constitutively expressed in mouse bone marrow cell-derived cultured MCs (BMCMCs), suggesting that IL-10 may influence MCs function. Indeed, we found that only IL-10 could influence upon BMCMCs function; IL-10 enhanced prolongation of survival, promoted IL-6 and/or IL-13 production dependently of STAT1 and STAT3, and suppressed tumor necrosis factor production independently of STAT1 and STAT3 on IgE-stimulated BMCMCs. Moreover, the IL-10-mediated enhancement of IL-6 production by IgE-stimulated BMCMCs promotes Th17 cell expansion. These results suggest that IL-10 has a dual role as an anti-inflammatory and pro-inflammatory cytokine in MCs functions. [ABSTRACT FROM AUTHOR]

This study aimed to clarify the effects of different types of gadolinium (Gd)-based contrast agents (GBCAs) and different T1 values of Gd-containing materials on the R1 value and magnetic susceptibility of quantitative susceptibility mapping (QSM). GBCA dilution phantoms were prepared using five types to of GBCA evaluate their effects. The effect of different T1 values of substances with Gd was assessed. A 3.0 T-MR scanner with a 20-channel head/neck coil was used to acquire the R1 map and QSM for the phantom. Linear regression analysis was performed to evaluate the relationship between Gd concentration and R1 or magnetic susceptibility for each phantom. An analysis of covariance (ANCOVA) was employed to assess the consistency of the slopes. Linear regression analysis showed that Gd concentration had a high coefficient of determination for R1 values and magnetic susceptibility (R2, 0.696–0.999; p < 0.001). ANCOVA showed significant differences in the slopes of R1 values when different GBCA types were used (p < 0.001), but no significant differences in the slopes for magnetic susceptibility (p = 0.719). Differences in surrounding T1 values significantly altered the intercepts and slopes of the measurements of R1 values and magnetic susceptibility (p < 0.001). The change in slope was smaller for magnetic susceptibility than for R1 values. Thus, while R1 was minimally affected by the GBCA type, it varied with surrounding tissue T1 values. QSM, however, was unaffected by the GBCA type and less influenced by T1 values, suggesting QSM may offer more quantitative measurements of Gd compared to R1 maps. [ABSTRACT FROM AUTHOR]

Background: The Greenhouse gas Observations of Biospheric and Local Emissions from the Upper sky (GOBLEU) is a new joint project by Japan Aerospace Exploration Agency (JAXA) and ANA HOLDING INC. (ANAHD), which operates ANA flights. GOBLEU aims to visualizes our climate mitigation effort progress in support of subnational climate mitigation by collecting greenhouse gas (GHG) data as well as relevant data for emissions (nitrous dioxide, NO2) and removals (Solar-Induced Fluorescence, SIF) from regular passenger flights. We developed a luggage-sized instrument based on the space remote-sensing techniques that JAXA has developed for Japan's Greenhouse gas Observing SATellite (GOSAT). The instrument can be conveniently installed on a coach-class passenger seat without modifying the seat or the aircraft. Results: The first GOBLEU observation was made on the flight from the Tokyo Haneda Airport to the Fukuoka Airport, with only the NO2 module activated. The collected high-spatial-resolution NO2 data were compared to that from the TROPOspheric Monitoring Instrument (TROPOMI) satellite and surface NO2 data from ground-based air quality monitoring stations. While GOBLEU and TROPOMI data shared the major concentration patterns largely driven by cities and large point sources, regardless of different observation times, we found fine-scale concentration pattern differences, which might be an indication of potential room for GOBLEU to bring in new emission information and thus is worth further examination. We also characterized the levels of NO2 spatial correlation that change over time. The quickly degrading correlation level of GOBLEU and TROPOMI suggests a potentially significant impact of the time difference between CO2 and NO2 as an emission marker and, thus, the significance of co-located observations planned by future space missions. Conclusions: GOBLEU proposes aircraft-based, cost-effective, frequent monitoring of greenhouse emissions by GOBLEU instruments carried on regular passenger aircraft. Theoretically, the GOBLEU instrument can be installed and operated in most commercially used passenger aircraft without modifications. JAXA and ANAHD wish to promote the observation technique by expanding the observation coverage and partnership to other countries by enhancing international cooperation under the Paris Agreement. [ABSTRACT FROM AUTHOR]

We report a case of a patient with distal bile duct cancer who presented with ocular pain and eye redness due to a liver abscess. The patient developed a liver abscess while waiting for surgery. Since Klebsiella pneumoniae with high viscosity was identified and imaging studies showed systemic infection, a diagnosis of klebsiella invasive syndrome was made. In addition, infectious intraocular inflammation was also observed at the same time. In addition to antibiotic therapy, vitrectomy and percutaneous transhepatic abscess drainage successfully normalized the inflammatory response and negative blood cultures were obtained. Thirty-four days after the start of treatment, surgery was performed and the postoperative course was uneventful, and the patient was discharged from the hospital on the 39th postoperative day. Forty-six months after that surgery, there has been no evidence of recurrence of cholangiocarcinoma or recurrence of infection, but unfortunately, vision loss in the right eye remains. Some Klebsiella pneumoniae are highly pathogenic and are often reported from Southeast Asia, and ocular pain and hyperemic symptoms are important physical findings. [ABSTRACT FROM AUTHOR]

Aneurysmal rupture is associated with wall thinning, but the mechanism is poorly understood. This study aimed to characterize the three-dimensional wall-thickness distributions of unruptured intracranial aneurysms. Five aneurysmal tissues were investigated using micro-computed tomography. First, the wall thickness was related to the aneurysmal wall appearances during surgery. The median wall thicknesses of the translucent and non-translucent walls were 50.56 and 155.93 µm, respectively (p < 0.05) with significant variation in the non-translucent wall thicknesses (p < 0.05). The three-dimensional observations characterized the spatial variation of wall thicknesses. Thin walls showed a uniform thickness profile ranging from 10 to 40 µm, whereas thick walls presented a peaked thickness profile ranging from 300 to 500 µm. In transition walls, the profile undulated due to the formation of focal thin/thick spots. Overall, the aneurysmal wall thicknesses were strongly site-dependent and spatially varied by 10 to 40 times within individual cases. Aneurysmal walls are exposed to wall stress driven by blood pressure. In theory, the magnitude of wall stress is inversely proportional to wall thickness. Thus, the observed spatial variation of wall thickness may increase the spatial variation of wall stress to a similar extent. The irregular wall thickness may yield stress concentration. The observed thin walls and focal thin spots may be caused by excessive wall stresses at the range of mechanical failure inducing wall injuries, such as microscopic tears, during aneurysmal enlargement. The present results suggested that blood pressure (wall stress) may have a potential of acting as a trigger of aneurysmal wall injury. [ABSTRACT FROM AUTHOR]

Group 2 innate lymphoid cells (ILC2s) are a subset of innate lymphocytes that produce type 2 cytokines, including IL-4, IL-5, and IL-13. GATA3 is a critical transcription factor for ILC2 development at multiple stages. However, when and how GATA3 is induced to the levels required for ILC2 development remains unclear. Herein, we identify ILC2-specific GATA3-related tandem super-enhancers (G3SE) that induce high GATA3 in ILC2-committed precursors. G3SE-deficient mice exhibit ILC2 deficiency in the bone marrow, lung, liver, and small intestine with minimal impact on other ILC lineages or Th2 cells. Single-cell RNA-sequencing and subsequent flow cytometry analysis show that GATA3 induction mechanism, which is required for entering the ILC2 stage, is lost in IL-17RB+PD-1− late ILC2-committed precursor stage in G3SE-deficient mice. Cnot6l, part of the CCR4-NOT deadenylase complex, is a possible GATA3 target during ILC2 development. Our findings implicate a stage-specific regulatory mechanism for GATA3 expression during ILC2 development. The transcription factor GATA3 is enhanced in innate lymphoid type 2 cells (ILC2). Here the authors characterize the super enhancer regions of GATA3 and show that these enhancers are required to drive GATA3 expression and stage specific ILC2 development. [ABSTRACT FROM AUTHOR]

Background: A chronic expanding hematoma is an uncommon entity described as an organized blood collection that increases in size after the initial hemorrhagic event without histological neoplastic features. The standard treatment is complete resection. To our knowledge, this is the first report of a chronic expanding hematoma mimicking a pancreatic cystic tumor that has been successfully resected utilizing a laparoscopic approach. Case presentation: We report the case of a 32-year-old man with a 10-cm chronic expanding hematoma that was preoperatively diagnosed as a cystic pancreatic tumor. Dynamic computed tomography revealed a cyst at the inferior part of the uncinate process of the pancreas without contrast enhancement. His blood biochemical data were within normal limits. The operation initially utilized a laparoscopic approach; however, the procedure was converted to hand-assisted laparoscopic surgery due to capsule adherence to surrounding organs and finally, enucleation of the tumor was performed. Pathological findings revealed a chronic expanding hematoma in the retroperitoneal space. Conclusion: Chronic expanding hematoma in the retroperitoneal space is so rare and sometimes adheres to the surrounding tissue. It is difficult to distinguish hematoma attaching pancreas and pancreatic cyst preoperatively. In rare cases such as this, hand-assisted laparoscopic surgery is a feasible, less invasive procedure for facilitating complete resection and preventing recurrence. [ABSTRACT FROM AUTHOR]

Many targeted cancer therapies rely on biomarkers assessed by scoring of immunohistochemically (IHC)-stained tissue, which is subjective, semiquantitative, and does not account for expression heterogeneity. We describe an image analysis-based method for quantitative continuous scoring (QCS) of digital whole-slide images acquired from baseline human epidermal growth factor receptor 2 (HER2) IHC-stained breast cancer tissue. Candidate signatures for patient stratification using QCS of HER2 expression on subcellular compartments were identified, addressing the spatial distribution of tumor cells and tumor-infiltrating lymphocytes. Using data from trastuzumab deruxtecan-treated patients with HER2-positive and HER2-negative breast cancer from a phase 1 study (NCT02564900; DS8201-A-J101; N = 151), QCS-based patient stratification showed longer progression-free survival (14.8 vs 8.6 months) with higher prevalence of patient selection (76.4 vs 56.9%) and a better cross-validated log-rank p value (0.026 vs 0.26) than manual scoring based on the American Society of Clinical Oncology / College of American Pathologists guidelines. QCS-based features enriched the HER2-negative subgroup by correctly predicting 20 of 26 responders. [ABSTRACT FROM AUTHOR]

To formulate the relationship between the dextrin hydrate concentration and T1 relaxation rate and create a magnetic resonance imaging (MRI) phantom with an arbitrary T1 value. Dextrin solution with nine different concentrations was prepared by dissolving 0–20 g (2.5 g increments) of dextrin in 25 g of purified water. The T1 values of the phantoms were measured using a 1.5 T MR scanner, and the relationship between the R1 value and dextrin concentration was regressed using linear and quadratic equations. Phantoms with concentrations adjusted to T1 values of 500, 1000, and 1500 ms were created from each regression equation, and the errors between the measured T1 and target values were evaluated. In addition, the temporal changes in the T1 and T2 values of the phantoms were also evaluated. The T1 and T2 values ranged from 367.4 ± 14.1 to 2577.6 ± 76.5 ms and 20.0 ± 0.9 to 1805.3 ± 8.3 ms, respectively. The linear and quadratic regression equations were y = 2.9631 x + 0.2043 and y = 1.8295 x 2 + 1.4995 x + 0.37 , with coefficients of determination of 0.9763 and 0.9954, respectively. The maximum errors were 12.3% and 2.1% for the linear and quadratic equations, respectively. The T1 value was maintained at a fluctuation rate of approximately 10% during the first 4 weeks. The T2 value decreased by approximately 20% after 4 weeks. MRI phantoms with arbitrary T1 values in the range of 500–1500 ms with an error within 2.1% can be created using dextrin, which can be used as human tissue-equivalent MRI phantoms for T1 of the grey or white matter of the brain, liver, pancreas, spleen, and prostate. [ABSTRACT FROM AUTHOR]

In agricultural pest management, the traditional insect population tracking in the case of several insect types is based on outsourced sticky paper traps that are checked periodically by a human operator. However, with the aid of the Internet of Things technology and machine learning, this type of manual monitoring can be automated. Even though great progress has been made in the field of insect pest detector models, the lack of sufficient amount of remote sensed trap images prevents their practical application. Beyond the lack of sufficient data, another issue is the large discrepancy between manually taken and remote sensed trap images (different illumination, quality, background, etc.). In order to improve those problems, this paper proposes three previously unused data augmentation approaches (gamma correction, bilateral filtering, and bit-plate slicing) which artificially enrich the training data and through this increase the generalization capability of deep object detectors on remote sensed trap images. Even with the application of the widely used geometric and texture-based augmentation techniques, the proposed methods can further increase the efficiency of object detector models. To demonstrate their efficiency, we used the Faster Region-based Convolutional Neural Network (R-CNN) and the You Look Only Once version 5 (YOLOv5) object detectors which have been trained on a small set of high-resolution, manually taken trap images while the test set consists of remote sensed images. The experimental results showed that the mean average precision (mAP) of the reference models significantly improved while in some cases their counting error was reduced to a third. [ABSTRACT FROM AUTHOR]

The surface spectral absorptivity of surface-whitened mortars due to the occurrence of efflorescence (i.e., mortars whose surface was covered with calcium carbonate) was measured, and the relationship between the spectral absorptivity and inspection capability of active thermography inspection was investigated. The spectral absorptivity of mortars increased significantly at a wavelength of approximately 3000 nm regardless of the presence/absence of the discoloration. Experiments for mortar specimens using optical lights with wavelengths in the visible, short wavelength, and medium/long wavelength ranges showed that the heating efficiency and defect detection capability of active thermography inspection were correlated with the surface spectral absorptivity, and were higher when long wavelength light was used as a heater. Defects in the surface-whitened mortar specimen were detected more efficiently when the specimen was heated using a CO2 laser, whose wavelength is in the long wavelength range, than when using an optical light having a wavelength in the visible/short wavelength range. [ABSTRACT FROM AUTHOR]

We prepared organic–inorganic layered perovskite-type compounds having a linear alkyl diamine (NH3CnH2nNH3)PbCl4 (n = 6: (1, 6-DHX)PbCl4, n = 7: (1,7-DHP)PbCl4, n = 8: (1,8-DIO)PbCl4, n = 9: (1,9-DIN)PbCl4, n = 10: (1,10-DID)PbCl4, n = 11: (1,11-DIU)PbCl4) and investigated their photoluminescence and scintillation characteristics. A broad band peak that should be attributed to self-trapped excitons (STEs) were observed at 555 nm ((1,6-DHX)PbCl4), 520 nm ((1,7-DHP)PbCl4), 525 nm ((1,8-DIO)PbCl4), 525 nm ((1,9-DIN)PbCl4), 550 nm ((1,10-DID)PbCl4), and 530 nm ((1,11-DIU)PbCl4) in scintillation. Also, they showed a scintillation decay time of 2.2 ns ((1,6-DHX)PbCl4), 3.0 ns ((1,7-DHP)PbCl4), 2.8 ns ((1,8-DIO)PbCl4), 5.6 ns ((1,9-DIN)PbCl4), 3.5 ns ((1,10-DID)PbCl4), and 4.7 ns ((1,11-DIU)PbCl4) due to the STE recombination. Further, the scintillation light yield of the (1,9-DIN)PbCl4 crystal was the highest (1,200 photons/5.5 MeV-α), and its value was higher than that of an undoped zinc oxide crystal. [ABSTRACT FROM AUTHOR]

The solid electrolytes with a low melting temperature are promising for the all-solid-state lithium batteries because such electrolytes enable the battery fabrication without high-temperature sintering (for example, ~ 1000 °C for oxide materials). In this study, a series of LiOH-Li2SO4 systems with different LiOH/Li2SO4 ratios is fabricated by melting LiOH and Li2SO4 at 430 °C, and their ion conduction properties are investigated. The stoichiometric compounds are obtained in 2.2LiOH‧Li2SO4 without segregation of LiOH and Li2SO4, which is rather different from the previously known composition (3LiOH‧Li2SO4). The deviation from this LiOH/Li2SO4 fraction results in a segregation of LiOH or Li2SO4. The conductivities of 2.2LiOH‧Li2SO4 with 5 mol% of Li3BO3 are 1.9 × 10−6 and 6.0 × 10−3 S/cm at 25 and 150 °C, respectively. The all-solid-state batteries are fabricated by hot pressing the solid electrolyte with Li(Ni0.3Co0.6Mn0.1)O2 (cathode) and graphite (anode) at 250 °C under 150 MPa. The contacts of the solid electrolyte with Li(Ni0.3Co0.6Mn0.1)O2 and graphite are intimate, and the by-products are not found at the interphase. The discharge capacities of 80 mAh/g are obtained for 100 cycles at 150 °C when the charging voltage is restricted to 3.95 V. The results of cyclic voltammetry measurement indicate the reductive decomposition of the solid electrolyte at 2.3 and 1.6 V. These reduction currents are decreased with cycling, suggesting the passivation of the anode interphase. On the other hand, the oxidation current is observed above 3.6 V which is not terminated during voltage cycling. In the battery fabrication process, high-temperature sintering is not necessary, and the dense contacts with electrode materials can be made by hot pressing at 250 °C. Furthermore, the batteries are constructed in a dry room where the dew point is maintained at − 40 °C. The present results suggest the potential of the LiOH-Li2SO4 as the solid electrolyte for all-solid-state lithium batteries. [ABSTRACT FROM AUTHOR]

Purpose: Mammography screening has increased the detection of subcentimeter breast cancers. The prognosis for estrogen receptor (ER)-positive and human epidermal growth factor receptor 2 (HER2)-negative T1a/bN0M0 breast cancers is excellent; however, the necessity of adjuvant endocrine therapy (ET) is uncertain. Methods: We evaluated the effectiveness of adjuvant ET in patients with ER-positive and HER2-negative T1a/bN0M0 breast cancer who underwent surgery from 2008 to 2012. Standard ET was administrated after surgery. The primary endpoint was the cumulative incidence of distant metastasis. All statistical tests were 2-sided. Results: Adjuvant ET was administered to 3991 (83%) of the 4758 eligible patients (1202 T1a [25.3%] and 3556 T1b [74.7%], diseases). The median follow-up period was 9.2 years. The 9-year cumulative incidence of distant metastasis was 1.5% with ET and 2.6% without ET (adjusted subdistribution hazard ratio [sHR], 0.54; 95% CI, 0.32–0.93). In multivariate analysis, the independent risk factors for distant metastasis were no history of ET, mastectomy, high-grade, and lymphatic invasion. The 9-year overall survival was 97.0% and 94.4% with and without ET, respectively (adjusted HR, 0.57; 95% CI, 0.39–0.83). In addition, adjuvant ET reduced the incidence of ipsilateral and contralateral breast cancer (9-year rates; 1.1% vs. 6.9%; sHR, 0.17, and 1.9% vs. 5.2%; sHR, 0.33). Conclusions: The prognosis was favorable in patients with ER-positive and HER2-negative T1a/bN0M0 breast cancer. Furthermore, adjuvant ET reduced the incidence of distant metastasis with minimal absolute risk difference. These findings support considering the omission of adjuvant ET, especially for patients with low-grade and no lymphatic invasion disease. [ABSTRACT FROM AUTHOR]

Aims: SP142 and 22C3 assays are approved companion diagnostic assays for anti-PD-1/PD-L1 therapy selection in metastatic triple-negative breast cancer (TNBC). The discordance in PD-L1 status between primary and metastatic tumors in the same patient has been poorly characterized. Here, we examined the concordance of PD-L1 status between the two assays and between primary tumors and metastases for each assay. Methods: We retrospectively evaluated tumor samples from 160 patients with TNBC, including 45 patients with paired primary and metastatic tumors. PD-L1 status was assessed using SP142 and 22C3 assays, to determine the immune cell (IC) score, tumor cell (TC) score (SP142 and 22C3), and combined proportion score (CPS: 22C3). Results: The concordance of PD-L1 positivity at diagnostic cutoffs for SP142 (IC ≥ 1) and 22C3 (CPS ≥ 10) was substantial (κ = 0.80) in primary tumors and moderate (κ = 0.60) in metastatic tumors. In comparison, between primary and metastatic tumors, the concordance with 22C3 was moderate (κ = 0.50), whereas that with SP142 was poor (κ = -0.03). Among patients who were PD-L1 negative for both assays in primary tumors, 7/30 (23.3%) were PD-L1 positive for both or either 22C3 or SP142 in the metastatic tumors. Conclusions: The inter-assay concordance of PD-L1 positivity at diagnostic cutoffs was substantial in primary tumors and moderate in metastatic tumors. Discordance between PD-L1 status in primary and metastatic tumors was frequently observed, especially with SP142. Some patients with a PD-L1-negative status in primary tumors may still be candidates for immunotherapy, depending on the PD-L1 status in their metastatic tumors. [ABSTRACT FROM AUTHOR]

Adjuvant therapy for patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative, node-positive, early breast cancer (EBC) remains challenging. The prognostic significance of HER2-low positivity in these patients is not fully understood. In our retrospective study, we analyzed 647 patients with HR-positive, HER2-negative, node-positive EBC, stratifying them into three cohorts based on axillary lymph node involvement, tumor size, and characteristics. Cohort 1 included patients with either ≥ 4 positive axillary lymph nodes or 1–3 positive nodes with histological grade 3 or tumor size ≥ 5 cm. Cohort 2 consisted of patients with 1–3 positive nodes, histological grade < 3, tumor size < 5 cm, and Ki-67 ≥ 20%. Cohort 3 comprised patients with 1–3 positive nodes, histological grade < 3, tumor size < 5 cm, and Ki-67 < 20%. We compared invasive disease-free survival (IDFS) and distant relapse-free survival (DRFS) between HER2-low (IHC1+ or IHC2+/FISH−) and HER2-zero (IHC0) groups in each cohort. In cohort 1, HER2-low patients exhibited significantly better 5-year IDFS (84.2% vs. 73.6%, p = 0.0213) and DRFS (88.2% vs. 79.8%, p = 0.0154). However, no significant differences were observed in cohorts 2 and 3. Our findings suggest HER2-low positivity as a prognostic factor in HR-positive, HER2-negative, and node-positive EBC. [ABSTRACT FROM AUTHOR]

The Mediterranean diet, which is characterized by high consumption of olive oil, prevents cardiovascular disease. Meanwhile, olive mill wastewater (OMWW), which is obtained as a byproduct during olive oil production, contains various promising bioactive components such as water-soluble polyphenols. Hydroxytyrosol (HT), the major polyphenol in OMWW, has anti-oxidative and anti-inflammatory properties; however, the atheroprotective effects of OMWW and HT remain to be fully understood. Here, we investigated the effect of OMWW and HT on atherogenesis. Male 8-week-old apolipoprotein E-deficient mice were fed a western-type diet supplemented with OMWW (0.30%w/w) or HT (0.02%w/w) for 20 weeks. The control group was fed a non-supplemented diet. OMWW and HT attenuated the development of atherosclerosis in the aortic arch as determined by Sudan IV staining (P < 0.01, respectively) without alteration of body weight, plasma lipid levels, and blood pressure. OMWW and HT also decreased the production of oxidative stress (P < 0.01, respectively) and the expression of NADPH oxidase subunits (e.g., NOX2 and p22phox) and inflammatory molecules (e.g. IL-1β and MCP-1) in the aorta. The results of in vitro experiments demonstrated that HT inhibited the expression of these molecules that were stimulated with LPS in RAW264.7 cells, murine macrophage-like cells. OMWW and HT similarly attenuated atherogenesis. HT is a major component of water-soluble polyphenols in OMWW, and it inhibited inflammatory activation of macrophages. Therefore, our results suggest that the atheroprotective effects of OMWW are at least partially attributable to the anti-inflammatory effects of HT. [ABSTRACT FROM AUTHOR]

A 65-year-old woman underwent living-donor liver transplantation (left-lobe graft: GWRW ratio, 0.54) for cirrhosis caused by autoimmune hepatitis. At 68 years, she was diagnosed with obstructive cholangitis due to stricture during a hepaticojejunostomy following impaired liver function. Endoscopic balloon dilation of anastomosis and placement of a plastic stent resulted in improved liver function. However, at 72 years, the patient experienced a flare-up of liver damage. The plastic stent had fallen out, and although endoscopic stenotic dilation was attempted, the anastomotic site was obstructed completely. Therefore, recanalization of the hepaticojejunostomy was attempted using a rendezvous technique. A percutaneous transhepatic biliary drainage tube was inserted through the B3 bile duct, and the complete obstructed anastomosis was confirmed by percutaneous transhepatic and transjejunal approaches. The anastomosis was reopened by excising the scarred tissues from the jejunal side using a 1.5-mm high-frequency knife. A 14-Fr. catheter for the internal fistula tube was percutaneously placed at the opened anastomosis to achieve anastomotic site recanalization. The patient's liver damage improved after the re-internalization, and no symptom recurrence such as obstructive cholangitis developed for 1 year. There are few reports of recanalization of the hepaticojejunostomy with a high-frequency knife. Herein, we report the case with a literature review. [ABSTRACT FROM AUTHOR]

Purpose: To analyze the appropriateness of primary response for anaphylaxis due to iodinated contrast media (ICM) or gadolinium-based contrast agents (GBCA). Materials and methods: This retrospective study included all patients in whom intravenous contrast agents (five types of ICMs and four types of GBCAs) were administered at our hospital between April 2016 and September 2021. For the patients who developed anaphylaxis, we obtained data on the time records of contrast injection, anaphylaxis onset, and intramuscular adrenaline (epinephrine) administration. Results: Of the 76,555 ICM and 30,731 GBCA administrations, anaphylaxis occurred in 49 cases (0.05%), and in 48 cases (98.0%) the onset was within 30 min after administration with widely distributed times (median, 7.5 min; interquartile range, 4.5–10.8 min; max, 26 min). Intramuscular adrenaline administration was performed in 43 cases (87.8%), and this was done within five minutes after the onset in 37 cases (75.5%). Only in 24 cases (49.0%), there were time records of both the onset and adrenaline administration (if performed). Conclusion: Anaphylaxis occurred within 30 min after contrast injection in the majority of the cases, but times were widely distributed. Only in 75.5% of cases, appropriate primary treatment was performed, and the importance of keeping exact time records in patients' charts should be re-emphasized. [ABSTRACT FROM AUTHOR]

Hepatic portal vein gas (HPVG) is caused by the influx of gastrointestinal gas into the intrahepatic portal vein as a result of gastrointestinal wall fragility due to ischemia or necrosis. Gastrointestinal tract necrosis is fatal in severe cases. We observed a case of food intake-induced acute gastric dilatation (AGD) in a healthy young male who developed HPVG and underwent conservative treatment. A 25-year-old male presented to our hospital with epigastric pain and nausea the day after excessive food intake. Computed tomography (CT) revealed gas along the intrahepatic portal vein and marked gastric dilatation with large food residue. AGD-induced HPVG was considered. Esophagogastroduodenoscopy (EGD) was not performed at this stage because of the risk of HPVG and AGD exacerbation, and the patient was followed up with intragastric decompression via a nasogastric tube. Food residue and approximately 2 L of liquid without blood were vomited 1 h after the nasogastric tube placement. His symptoms improved after the vomiting episode. An EGD was performed 2 days after undergoing CT. Endoscopic findings revealed extensive erosions and the presence of a whitish coat extending from the fornix to the lower body of the stomach, indicating AGD. HPVG disappeared on the CT scan taken during EGD. Thereafter, symptom relapse and HPVG recurrence were not observed. [ABSTRACT FROM AUTHOR]

Plasma membrane rupture (PMR) in dying cells undergoing pyroptosis or apoptosis requires the cell-surface protein NINJ11. PMR releases pro-inflammatory cytoplasmic molecules, collectively called damage-associated molecular patterns (DAMPs), that activate immune cells. Therefore, inhibiting NINJ1 and PMR may limit the inflammation that is associated with excessive cell death. Here we describe an anti-NINJ1 monoclonal antibody that specifically targets mouse NINJ1 and blocks oligomerization of NINJ1, preventing PMR. Electron microscopy studies showed that this antibody prevents NINJ1 from forming oligomeric filaments. In mice, inhibition of NINJ1 or Ninj1 deficiency ameliorated hepatocellular PMR induced with TNF plus d-galactosamine, concanavalin A, Jo2 anti-Fas agonist antibody or ischaemia–reperfusion injury. Accordingly, serum levels of lactate dehydrogenase, the liver enzymes alanine aminotransaminase and aspartate aminotransferase, and the DAMPs interleukin 18 and HMGB1 were reduced. Moreover, in the liver ischaemia–reperfusion injury model, there was an attendant reduction in neutrophil infiltration. These data indicate that NINJ1 mediates PMR and inflammation in diseases driven by aberrant hepatocellular death.A monoclonal antibody that binds NINJ1 and inhibits NINJ1 oligomerization prevents plasma membrane rupture in dying cells, resulting in decreased inflammation of surrounding tissue in mice. [ABSTRACT FROM AUTHOR]

Purpose: The impact of progesterone receptor (PR) status on the prognosis of breast cancer after isolated locoregional recurrence (ILRR) remains unclear. This study evaluated the impact of clinicopathologic factors, including PR status of ILRR, on distant metastasis (DM) after ILRR. Methods: We retrospectively identified 306 patients with ILRR diagnosed at the National Cancer Center Hospital between 1993 and 2021 from the database. Cox proportional hazards analysis was performed to examine factors associated with DM after ILRR. We developed a risk prediction model based on the number of detected risk factors and estimated survival curves using the Kaplan–Meier method. Results: During a median follow-up time of 4.7 years after ILRR diagnosis, 86 patients developed DM, and 50 died. Multivariate analysis revealed that seven risk factors were associated with poor distant metastasis-free survival (DMFS): estrogen receptor-positive/PR-negative/human epidermal growth factor receptor 2-negative ILRR, short disease-free interval, recurrence site other than ipsilateral breast, no-resection of ILRR tumor, chemotherapy for the primary tumor, nodal stage in the primary tumor, and no endocrine therapy for ILRR. The predictive model classified patients into 4 groups based on the number of risk factors: low-, intermediate-, high-, and the highest-risk groups with 0 to 1, 2, 3 to 4, and 5 to 7 factors, respectively. This revealed significant variation in DMFS among the groups. A higher number of the risk factors was associated with poorer DMFS. Conclusion: Our prediction model, which considered the ILRR receptor status, may contribute to the development of a treatment strategy for ILRR. [ABSTRACT FROM AUTHOR]

Chronic pain and attention-deficit hyperactivity disorder (ADHD) frequently coexist. However, the common pathology is still unclear. Attenuated noradrenergic endogenous analgesia can produce acute pain chronification, and dysfunction of noradrenergic systems in the nervous system is relevant to ADHD symptoms. Noxious stimuli-induced analgesia (NSIA) is measured to estimate noradrenergic endogenous analgesia in spontaneously hypertensive rats (SHR) as an ADHD model and control. Recovery of pain-related behaviors after paw incision was assessed. Contributions of noradrenergic systems were examined by in vivo microdialysis and immunohistochemistry. The SHR showed attenuated NSIA and needed a more extended period for recovery from acute pain. These results suggest ADHD patients exhibit acute pain chronification due to pre-existing attenuated noradrenergic endogenous analgesia. Immunohistochemistry suggests abnormal noradrenaline turnover and downregulation of the target receptor (alpha2a adrenoceptor). Standard ADHD treatment with atomoxetine restored NSIA and shortened the duration of hypersensitivity after the surgery in the SHR. NSIA protocol activated the locus coeruleus, the origin of spinal noradrenaline, of both strains, but only the control exhibited an increase in spinal noradrenaline. This result suggests dysfunction in the noradrenaline-releasing process and can be recognized as a novel mechanism of attenuation of noradrenergic endogenous analgesia. [ABSTRACT FROM AUTHOR]

Type 2 diabetes mellitus (T2D) in male KK-Ay and B6-Ay mice is typically associated with hyperinsulinemia, whereas male DDD-Ay mice exhibit a marked decrease in circulating insulin levels due to the loss of pancreatic islet β-cells. T2D in male DDD-Ay mice is linked to Nidd/DDD, a significant quantitative trait locus (QTL) mapped with a 95% confidence interval (CI) between 112.44 and 151.47 Mbp on chromosome 4. Several T2D QTLs involving Nidd/SJL and Nidd/DBA have been identified on this chromosome; however, their allelic relationships remain unclear. In this study, two sets of male F2-Ay mice produced by crossing C57BL/6J and DDD-Ay mice, and C3H/HeJ and DDD-Ay mice, were used to narrow the 95% CI of the Nidd/DDD to a 9.4 Mbp interval between 114.65 and 125.05 Mbp. Candidate genes underlying Nidd/DDD were identified, assuming that the causative variant is a nonsynonymous single nucleotide variant (nsSNV). The analysis identified 48 potential candidate nsSNVs unique to DDD-Ay mice compared to those in KK, B6, C3H, and DBA mice. Among these nsSNVs, 18 were identified in olfactory receptor genes, which have recently been implicated in the pathogenesis of T2D. The 9.4 Mbp region also contained Zfp69, a potential causative gene for Nidd/SJL, suggesting that Nidd/DDD could be allelic to Nidd/SJL but not to Nidd/DBA. In summary, the findings of this study provide insights into the allelic relationships between T2D QTLs on murine chromosome 4 and their underlying causative genetic variations. [ABSTRACT FROM AUTHOR]

Background: Chemotherapy and radiotherapy were postulated to induce an inflamed tumour microenvironment. We aimed to evaluate the effects of adjuvant chemotherapy/radiotherapy on tumour-infiltrating lymphocytes (TILs) and programmed death-ligand 1 (PD-L1) expression in metastatic breast cancer. Methods: We identified paired primary and metastatic tumours in 85 patients with breast cancer. Stromal TILs were assessed according to international guidelines. PD-L1 expression was evaluated using the VENTANA SP142 assay. Results: TILs were significantly lower in metastatic tumours than in primary tumours (12.2 vs. 8.3%, p = 0.049). PD-L1 positivity was similar between primary and metastatic tumours (21.2 vs. 14.1%, p = 0.23). TILs were significantly lower in patients who received adjuvant chemotherapy than in those who did not (−9.07 vs. 1.19%, p = 0.01). However, radiotherapy had no significant effect on TILs (p = 0.44). Decreased TILs predicted worse post-recurrence survival (hazard ratio, 2.94; 95% confidence interval [CI]: 1.41–6.13, p = 0.003), while increased TILs was associated with a better prognosis (HR, 0.12; 95% CI: 0.02–0.08, p = 0.04). Conclusions: TILs decreased in metastatic tumours, particularly in patients who relapsed after adjuvant chemotherapy. Changes in TILs from primary to metastatic sites could be a prognostic factor after recurrence. [ABSTRACT FROM AUTHOR]

Purpose: Male breast cancer (MBC) is a rare cancer accounting for only 1% of all male cancers and is, therefore, poorly studied. We aimed to characterize the subtypes of MBC in Japanese patients based on genetic profiling, the presence of tumor-infiltrating cells, and the expression of immunohistochemical markers. Methods: This retrospective study included 103 patients with MBC diagnosed between January 2009 and December 2019 at various hospitals in Japan. Clinicopathological patient characteristics were obtained from medical records, and formalin-fixed paraffin-embedded tissue specimens were analyzed for histological markers, mutations of 126 genes, BRCA1 methylation, and stromal tumor-infiltrating lymphocytes. Results: The median patient age was 71 (range 31–92) years. T1-stage tumors were the most frequent (47.6%), and most were node negative (77.7%). The majority of tumors were positive for estrogen receptor (98.1%), progesterone receptor (95.1%), and androgen receptor (96.1%), and BRCA2 was the most frequently mutated gene (12.6%). The most common treatment was surgery (99.0%), either total mastectomy (91.1%) or partial mastectomy (7.0%). Survival analysis showed a 5-year recurrence-free survival rate of 64.4% (95% confidence interval [CI] 46.7–88.8) and a 5-year overall survival rate of 54.3% (95% CI 24.1–100.0). Conclusion: Japanese MBC is characterized by a high rate of hormonal receptor positivity and BRCA2 somatic mutation. Due to the observed clinicopathological differences in MBC between the Western countries and Japan, further prospective studies are needed to evaluate the most suitable treatment strategies. [ABSTRACT FROM AUTHOR]

Purpose: In the 5th edition of the World Health Organization classification, appendiceal goblet cell adenocarcinoma (GCA) is categorized separately from neuroendocrine tumors and other appendiceal adenocarcinomas. We clarified the clinicopathological characteristics of Japanese appendiceal GCA. Methods: We designed a retrospective multicenter cohort study and retrieved the data of patients with appendiceal neoplasms and histologically diagnosed appendiceal goblet cell carcinoid (GCC) treated from January 2000 to December 2017 in Japan. The available GCC slides were reviewed and diagnosed with a new grading system of GCA. Results: A total of 922 patients from 43 institutions were enrolled; of these, 32 cases were patients with GCC (3.5%), and 20 cases were ultimately analyzed. The 5-year survival rate was 61.4% (95% confidence interval: 27.4–83.2), and the median survival time was 93.1 months. For peritoneal metastasis, regional lymph node metastasis was a significant factor (p = 0.04), and Grade 3 was a potential factor (p = 0.07). No peritoneal metastasis was observed in either T1/2 patients (n = 2) or Grade 1 patients (n = 4). We were unable to detect any significant factors associated with regional lymph node metastasis. Conclusion: For peritoneal metastasis, regional lymph node metastasis was a significant factor, and Grade 3 was a potential factor. [ABSTRACT FROM AUTHOR]

A heavily T2-weighted FLAIR (hT2W-FLAIR) may have a potential to visualize very low concentration of gadolinium (Gd)-based contrast agents (GBCAs), owing to the water-suppression pulse and the decreased parenchymal signal due to a long echo time (TE). However, the optimal TE setting has not been well established. Our study aimed to elucidate the optimal TE for visualizing very low concentrations of GBCA in a phantom study. We employed phantoms made of diluted gadobutrol (Gd-BTDO3A) and purified water (4–128 µM), simulating cerebrospinal fluid (CSF), gray matter and white matter. The hT2W-FLAIR images were acquired using a 1.5-T MRI scanner, and the TE was changed in 100 ms increments from 100 to 800 ms. The acquired images were evaluated with the contrast-to-noise ratio (CNR) for the CSF phantom. The CNRs of the gray and white matter decreased steeply when the TE exceeded. However, the CNRs of GBCA did not depend on the TE setting for all concentrations, and were significantly higher than those of the gray or white matter at the TE of 500–800 ms for 32–128 µM (p < 0.05). At a TE of 700 ms, the CNR of GBCA of 16 µM was significantly higher than those of the gray or white matter (p < 0.05). The optimal TE of the hT2W-FLAIR sequence for detecting very low concentration of GBCA was 700 ms, and the signal intensity of GBCA was higher than that of gray or white matter at the lowest concentration of 16 µM. [ABSTRACT FROM AUTHOR]

Epithelial cells control a variety of immune cells by secreting cytokines to maintain tissue homeostasis on mucosal surfaces. Regulatory T (Treg) cells are essential for immune homeostasis and for preventing tissue inflammation; however, the precise molecular mechanisms by which epithelial cell-derived cytokines function on Treg cells in the epithelial tissues are not well understood. Here, we show that peripheral Treg cells preferentially respond to thymic stromal lymphoprotein (TSLP). Although TSLP does not affect thymic Treg differentiation, TSLP receptor-deficient induced Treg cells derived from naïve CD4+ T cells are less activated in an adoptive transfer model of colitis. Mechanistically, TSLP activates induced Treg cells partially through mTORC1 activation and fatty acid uptake. Thus, TSLP modulates the activation status of induced Treg through the enhanced uptake of fatty acids to maintain homeostasis in the large intestine. [ABSTRACT FROM AUTHOR]

Purpose: Stromal tumor-infiltrating lymphocytes (TILs) are independent prognostic factors in systemically untreated early-stage triple-negative breast cancer (TNBC). Other immune biomarkers including CD8, CD20, programmed cell death-ligand 1 (PD-L1), and tertiary lymphoid structures (TLS) are also reported to be associated with prognosis. However, whether combining other immune biomarkers with TILs would allow for further prognostic stratification is unknown. Methods: We retrospectively analyzed 125 patients with early-stage TNBC not receiving perioperative chemotherapy. Stromal TILs and TLS were evaluated on hematoxylin–eosin slides. PD-L1 expression was evaluated using the SP142 assay. CD8 and CD20 were assessed by immunohistochemistry and counted by digital pathology. Results: Immune biomarker levels were positively correlated (p < 0.001). Adding CD8 and PD-L1 to multivariable analysis including clinicopathological factors (stage and histological grade) and TILs significantly improved the prognostic model (likelihood ratio χ2 = 9.24, p = 0.01). In Cox regression analysis, high CD8 was significantly associated with better prognosis [hazard ratio (HR) 0.69, 95% confidence interval (CI) 0.48–0.98, p = 0.04], and PD-L1 positivity was significantly associated with worse prognosis (HR 4.33, 95%CI 1.57–11.99, p = 0.005). Patients with high CD8/PD–L1 (–) tumors had the most favorable prognosis [5 year invasive disease-free survival (iDFS), 100%], while patients with low CD8/PD-L1(+) tumors had the worst prognosis (5 year iDFS, 33.3%). Conclusion: CD8 and PD-L1 levels add prognostic information beyond TILs for early-stage TNBC not receiving perioperative chemotherapy. CD8–positive T cells and PD-L1 may be useful for prognostic stratification and in designing future clinical trials of TNBC. [ABSTRACT FROM AUTHOR]

Purpose: Extracellular acidification is a major component of tissue inflammation, including airway inflammation. The extracellular proton-sensing mechanisms are inherent in various cells including airway structural cells, although their physiological and pathophysiological roles in bronchial smooth muscles (BSMs) are not fully understood. In the present study, to explore the functional role of extracellular acidification on the BSM contraction, the isolated mouse BSMs were exposed to acidic pH under contractile stimulation. Methods and Results: The RT-PCR analyses revealed that the proton-sensing G protein-coupled receptors were expressed both in mouse BSMs and cultured human BSM cells. In the mouse BSMs, change in the extracellular pH from 8.0 to 6.8 caused an augmentation of contraction induced by acetylcholine. Interestingly, the acidic pH-induced BSM hyper-contraction was further augmented in the mice that were sensitized and repeatedly challenged with ovalbumin antigen. In this animal model of asthma, upregulations of G protein-coupled receptor 68 (GPR68) and GPR65, that were believed to be coupled with Gq and Gs proteins respectively, were observed, indicating that the acidic pH could cause hyper-contraction probably via an activation of GPR68. However, psychosine, a putative antagonist for GPR68, failed to block the acidic pH-induced responses. Conclusion: These findings suggest that extracellular acidification contributes to the airway hyperresponsiveness, a characteristic feature of bronchial asthma. Further studies are required to identify the receptor(s) responsible for sensing extracellular protons in BSM cells. [ABSTRACT FROM AUTHOR]

Background: Emphysematous pancreatitis is acute pancreatitis associated with emphysema based on imaging studies and has been considered a subtype of necrotizing pancreatitis. Although some recent studies have reported the successful use of conservative treatment, it is still considered a serious condition. Computed tomography (CT) scan is useful in identifying emphysema associated with acute pancreatitis; however, whether the presence of emphysema correlates with the severity of pancreatitis remains controversial. In this study, we managed two cases of severe acute pancreatitis complicated with retroperitoneal emphysema successfully by treatment with lavage and drainage. Case presentation: Case 1: A 76-year-old man was referred to our hospital after being diagnosed with acute pancreatitis. At post-admission, his abdominal symptoms worsened, and a repeat CT scan revealed increased retroperitoneal gas. Due to the high risk for gastrointestinal tract perforation, emergent laparotomy was performed. Fat necrosis was observed on the anterior surface of the pancreas, and a diagnosis of acute necrotizing pancreatitis with retroperitoneal emphysema was made. Thus, retroperitoneal drainage was performed. Case 2: A 50-year-old woman developed anaphylactic shock during the induction of general anesthesia for lumbar spine surgery, and peritoneal irritation symptoms and hypotension occurred on the same day. Contrast-enhanced CT scan showed necrotic changes in the pancreatic body and emphysema surrounding the pancreas. Therefore, she was diagnosed with acute necrotizing pancreatitis with retroperitoneal emphysema, and retroperitoneal cavity lavage and drainage were performed. In the second case, the intraperitoneal abscess occurred postoperatively, requiring time for drainage treatment. Both patients showed no significant postoperative course problems and were discharged on postoperative days 18 and 108, respectively. Conclusion: Acute pancreatitis with emphysema from the acute phase highly indicates severe necrotizing pancreatitis. Surgical drainage should be chosen without hesitation in necrotizing pancreatitis with emphysema from early onset. [ABSTRACT FROM AUTHOR]

Background: Primary tumor location is considered a predictor of overall survival (OS) in RAS wild-type (WT) metastatic colorectal cancer (mCRC) treated with bevacizumab (BEV) or an anti-epidermal growth factor antibody (cetuximab or panitumumab [CET/PAN]) as first-line molecularly targeted therapy. BEV is recommended for right-sided mCRC and CET/PAN for left-sided mCRC based on post-hoc analyses of clinical trial data, but real-world evidence is lacking. Methods: We retrospectively collected data of patients who started BEV or CET/PAN plus 5-fluorouracil-based doublet chemotherapy between January 2013 and December 2016 as first-line treatment for RAS WT mCRC at any of 24 Japanese institutions. OS was compared between the BEV and CET/PAN groups according to primary tumor location by Cox multivariate regression analysis in the full cohort and in a propensity score-matched cohort. Results: In total, 935 patients were enrolled. Median OS was 24.6 months with BEV and 20.9 months with CET/PAN in right-sided mCRC (n = 213; adjusted hazard ratio [HR] 0.73, 95% confidence interval [CI] 0.50–1.06) and 35.7 months and 30.0 months, respectively, in left-sided mCRC (n = 722; adjusted HR 0.92, 95% CI 0.74–1.13). In the propensity score-matched cohort, OS was significantly better in the BEV group than in the CET/PAN group in right-sided mCRC (HR 0.52, 95% CI 0.28–0.96) but was not significantly different in left-sided mCRC (HR 0.78, 95% CI 0.53–1.07). Conclusion: Real-world data showed that OS was better with BEV than with CET/PAN in right-sided mCRC. However, there was no significant difference in OS in left-sided mCRC. [ABSTRACT FROM AUTHOR]

Administration of local anesthetics, such as lidocaine, in the perioperative period improves outcomes of cancer patients. However, its precise mechanism is still unresolved. The growth of human cancer cell lines, including HeLa cells, are suppressed by lidocaine treatment. We identified that growth differentiation factor-15 (GDF-15) was commonly upregulated in lidocaine-treated cancer cell lines. GDF-15 is a divergent member of the transforming growth factor-β (TGF-β) superfamily and it is produced as an unprocessed pro-protein form and then cleaved to generate a mature form. In lidocaine-treated HeLa cells, increased production of GDF-15 in the endoplasmic reticulum (ER) was observed and unprocessed pro-protein form of GDF-15 was secreted extracellularly. Further, lidocaine induced apoptosis and apoptosis-inducible Tribbles homologue 3 (TRIB3) was also commonly upregulated in lidocaine-treated cancer cell lines. In addition, transcription factor C/EBP homologous protein (CHOP), which is a positive regulator of not only GDF-15 but TRIB3 was also induced by lidocaine. Lidocaine-induced growth suppression and apoptosis was suppressed by knockdown of GDF-15 or TRIB3 expression by small interference RNA (siRNA). These observations suggest that lidocaine suppresses the growth of cancer cells through increasing GDF-15 and TRIB3 expression, suggesting its potential application as cancer therapy. [ABSTRACT FROM AUTHOR]

This study applies the models describing the effect of a neutrally stratified high-Reynolds-number boundary layer on peak wind estimation. A neutrally stratified atmosphere was simulated by ideal large-eddy simulations. The peak factor (PF) model successfully predicted the dependence of the PF on the duration and the evaluation time based on a spectral model containing k - 1 slopes at low frequencies. Time-dependent wind peak emergence was evaluated considering the amplitude modulation (AM) concept. For a large part of the atmospheric surface layer, the deviation of the time-dependent mean wind speed played a key role in peak modulation. The effect of a small-scale fluctuation cycle on peak modulation was found to be pronounced, specifically near the surface. It was possible to construct a predictive indicator of a peak event arrival based on the existing predictive model by AM. [ABSTRACT FROM AUTHOR]

The streptavidin–biotin system is known to have a very high affinity and specificity and is widely used in biochemical immunoassays and diagnostics. However, this method is affected by endogenous D-biotin in serum sample measurements (biotin interference). While several efforts using alternative high-affinity binding systems (e.g., genetically modified streptavidin and biotin derivatives) have been attempted, these efforts have all led to reduction in affinity. To solve this interference issue, the enantiomer of streptavidin was synthesized, which enabled specific binding to L-biotin. We successfully obtained a functional streptavidin molecule by peptide synthesis using D-amino acids and an in vitro folding technique. Several characterizations, including size exclusion chromatography (SEC), circular dichroism spectra (CD), and heat denaturation experiments collectively confirmed the higher-order enantiomer of natural streptavidin had been formed with comparable stability to the natural protein. L-biotin specific binding of this novel molecule enabled us to avoid biotin interference in affinity measurements using the Biacore system and enzyme-linked immunosorbent assay (ELISA). We propose the enantiomer of streptavidin as a potential candidate to replace the natural streptavidin–biotin system, even for in vivo use. [ABSTRACT FROM AUTHOR]

Introduction and hypothesis: Directed pushing while using the Valsalva maneuver is shown to lead to bladder neck descent, especially in women with urinary incontinence (UI). There is insufficient evidence about the benefits or adverse effects between the pushing technique during the second stage of labor and urinary incontinence postpartum. The objective of this study was to evaluate the effects of the pushing technique for women during labor on postpartum UI and birth outcomes. Methods: Scientific databases were searched for studies relating to postpartum urinary incontinence and birth outcomes when the pushing technique was used from 1986 until 2020. RCTs that assessed healthy primiparas who used the pushing technique in the second stage of labor were included. In accordance with Cochrane Handbook guidelines, risk of bias was assessed and meta-analyzed. Certainty of evidence was assessed using the GRADE approach. Results: Seventeen RCTs (4606 primiparas) were included. The change in UI scores from baseline to postpartum was significantly lower as a result of spontaneous pushing (two studies; 867 primiparas; standardized mean difference: SMD –0.18, 95% CI –0.31 to –0.04). Although women were in the recumbent position during the second stage, directed pushing group showed a significantly shorter labor by 21.39 min compared with the spontaneous pushing group: there was no significant difference in the duration of the second stage of labor between groups. Conclusions: Primiparas who were in the upright position and who experienced spontaneous pushing during the second stage of labor could reduce their UI score from baseline to postpartum. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to describe the MRI findings of epithelial-myoepithelial carcinoma (EMC) of the parotid gland. Materials and methods: Seven patients (four males and three females) aged 40–86 years (mean age, 64 years) with histologically proven EMC of the parotid gland who underwent surgical resection after preoperative MRI were enrolled. MRI images were retrospectively reviewed and contrasted with pathological findings. Results: Five patients (71%) had predominantly solid lesions, and two (29%) had predominantly cystic lesions. All seven lesions had well-demarcated margins and capsules without the invasion of adjacent structures. The capsules were incomplete in five lesions (71%) and complete in two (29%). Four lesions (57%) exhibited a multinodular structure with internal septa. Cystic components were observed in three lesions (43%). On T1-weighted images, the solid components were frequently homogeneous (5/7, 71%), and demonstrated isointensity in five lesions (71%) and hypointensity in two (29%) relative to the spinal cord. On T2-weighted images, the solid components were usually heterogeneous (6/7, 86%), and demonstrated hyperintensity in five lesions (71%) and isointensity in two (29%) relative to the spinal cord. The mean apparent diffusion coefficient value of the solid components was 0.967 × 10−3 mm2/s. Conclusion: Parotid gland EMCs usually appeared as predominantly solid lesions with well-demarcated margins and capsules. A multinodular structure with internal septa was characteristics of EMCs. [ABSTRACT FROM AUTHOR]

Advancement in nanotechnology to a large extent depends on the ability to manipulate materials at the atomistic level, including positioning single atoms on the active sites of the surfaces of interest, promoting strong chemical bonding. Here, we report a long-time confinement of a single Ag atom inside a corner hole (CH) of the technologically relevant Si(111)-7×7 surface, which has comparable size as a fullerene C60 molecule with a single dangling bond at the bottom center. Experiments reveal that a set of 17 Ag atoms stays entrapped in the CH for the entire duration of experiment, 4 days and 7 h. Warming up the surface to about 150 °C degrees forces the Ag atoms out of the CH within a few minutes. The processes of entrapment and diffusion are temperature dependent. Theoretical calculations based on density functional theory support the experimental results confirming the highest adsorption energy at the CH for the Ag atom, and suggest that other elements such as Li, Na, Cu, Au, F and I may display similar behavior. The capability of atomic manipulation at room temperature makes this effect particularly attractive for building single atom devices and possibly developing new engineering and nano-manufacturing methods. Positioning and trapping single atoms at specific sites of surfaces is a challenging goal that can advance the development of single atom devices. Here the authors demonstrate that single Ag atoms are trapped inside corner holes of the Si(111)-7×7 surface for more than 4 days at room temperature, and suggest that this behavior may be shared by other elements. [ABSTRACT FROM AUTHOR]

The most serious adverse effect of anthracycline chemotherapy is progressive dose-dependent left ventricular (LV) dysfunction, and a total cumulative doxorubicin dose ≥ 240 mg/m2 has been classified as putting patients at high risk for developing cardiac dysfunction. Hypertension is the single most important risk factor for heart failure and chemotherapy-induced LV dysfunction, but the effect of hypertension on the total cumulative doxorubicin dose to prevent the development of LV dysfunction in patients scheduled for anthracycline chemotherapy remains uncertain. The aim of this study was to investigate the effect of hypertension on the optimal total cumulative anthracycline dose to prevent the development of LV dysfunction in patients with malignant lymphoma. We retrospectively studied 92 patients with malignant lymphoma and preserved LV ejection fraction (LVEF) who underwent anthracycline chemotherapy. Echocardiography was performed before and 2 months after anthracycline chemotherapy. LV hypertrophy (LVH) was defined as concentric hypertrophy, and LV dysfunction after chemotherapy as a relative decrease in LVEF ≥ 5%. The cutoff value of the total cumulative doxorubicin dose for the development of LV dysfunction was lower for hypertensive patients (n = 23) than for non-hypertensive patients (n = 69) (259.3 mg/m2 vs. 358.9 mg/m2). Importantly, the cutoff value of the total cumulative doxorubicin dose to prevent the development of LV dysfunction in hypertensive patients with LVH was even lower at 40.1 mg/m2. A lower cumulative anthracycline dose can cause LV dysfunction in hypertensive patients with malignant lymphoma, especially when complicated by LVH. Our findings can thus be expected to have clinical implications for better management of such patients. [ABSTRACT FROM AUTHOR]

Purpose: We aimed to examine whether cardiorespiratory fitness and leg strength can be estimated based on their relationship with physical performance tests in Japanese breast cancer survivors. Methods: Participants were 50 sedentary women aged 20 to 59 years who have received breast surgery in the past 2 to 13 months after diagnosis of invasive breast cancer (stage I-IIa). Cardiorespiratory fitness and leg strength were measured by peak oxygen consumption (VO2peak), and one-repetition maximum for leg press (leg press 1RM). Physical performance tests were performed 6-min walk test, chair stand test, and grip strength. Using multiple regression analysis, we developed prediction equations for VO2peak and leg strength based on their associations with the physical performance tests. The validity of the estimation equations was assessed using Bland–Altman plots. Results: Mean age, VO2peak, and leg press 1RM were 48 ± 6 years, 25.0 ± 3.6 mL/kg/min, and 95 ± 32 kg, respectively. Multiple regression analysis yielded 6-min walk test distance, age, height, and body weight as predictors of VO2peak. Measured VO2peak and predicted VO2peak showed a moderate positive correlation (r = 0.463, p < 0.001). Chair stand test, grip strength, age, height, and body weight were selected as predictors of leg press 1RM. There was a strong positive correlation between predicted and measured leg press 1RM (r = 0.754, p < 0.001). Conclusion: The results suggest that leg strength can be predicted using physical performance tests. However, further examination may be needed to determine whether cardiorespiratory fitness can be predicted based on 6-min walk test. [ABSTRACT FROM AUTHOR]

Purpose: The optimal timing for starting lenvatinib treatment in patients with radioiodine-refractory differentiated thyroid cancer (RR-DTC) has long been controversial because of the relatively slow-growing nature of differentiated thyroid cancer. The aim of this study was to establish a scoring system using known clinical factors to simplify decision-making in when to start lenvatinib in RR-DTC patients. Methods: We retrospectively analyzed RR-DTC patients treated with lenvatinib. We developed the clinical indication scoring algorithm on the basis of age, tumor-related symptoms, histology, metastatic sites, neutrophil-to-lymphocyte ratio, size of lung metastases, baseline sum of tumor diameters, and tumor-volume doubling time that was used to categorize patients into low-, intermediate-, and high-risk groups. Results: A total of 59 patients were analyzed; 13 low-risk, 36 intermediate-risk, and 10 high-risk. The respective median progression-free survival from the initiation of lenvatinib was 93.7 months in the low-risk group, 20.3 months in the intermediate-risk group, and 6.2 months in the high-risk group (p < 0.02). Patients in the high-risk group had significantly worse overall survival compared with those in the low-risk (hazard ratio [HR] 6.59, 95% confidence interval [CI] 1.25–34.90, p < 0.03) or intermediate-risk (HR 2.99, 95% CI 1.03–8.63, p < 0.05) group. Using our proposed algorithm, patients in the intermediate-risk group showed treatment outcomes similar to that were observed in the pivotal trial of lenvatinib, and were the optimal patients to start lenvatinib. Conclusion: Our proposed scoring system can separate treatment outcomes and prognosis of RR-DTC patients treated with lenvatinib. This simple algorithm can be helpful for oncologists in deciding whether to start lenvatinib treatment in patients with RR-DTC. [ABSTRACT FROM AUTHOR]

Ampullary carcinomas of the duodenum are uncommon. Moreover, the diversity in the clinical outcomes of these patients makes it difficult to interpret previous studies and clinical trial results. The difficulty in proper staging of ampullary carcinomas, especially with regard to the T category of the tumor in the TNM system, reflects the anatomic complexity and non-uniform histopathologic subtypes. One major reason for this difficulty in interpretation is that the tumors may arise from any of the three epithelia (duodenal, biliary, or pancreatic) that converge at this location. Generally, ampullary carcinomas are classified into intestinal and pancreaticobiliary types based on morphology and immunohistochemical features. While many studies have described their specific characteristics and clinical impact, the prognostic value of these subtypes is controversial. In recent years, whole-exome sequencing analyses have advanced our understanding of the genomic overview of ampullary carcinoma. Gene mutations serve as prognostic and predictive biomarkers for this disease. Therefore, basic knowledge of the genomic profile of ampullary carcinomas is required for surgeons to understand how best to apply precision medicine as well as surgery and adjuvant therapies. This review provides an overview of the current basic and clinical issues of ampullary carcinoma. [ABSTRACT FROM AUTHOR]